EP2861301A2 - Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble salt - Google Patents
Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble saltInfo
- Publication number
- EP2861301A2 EP2861301A2 EP13733396.9A EP13733396A EP2861301A2 EP 2861301 A2 EP2861301 A2 EP 2861301A2 EP 13733396 A EP13733396 A EP 13733396A EP 2861301 A2 EP2861301 A2 EP 2861301A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- composition according
- hyaluronic acid
- sucrose octasulfate
- soluble salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 349
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 159
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 title claims abstract description 157
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 154
- 150000003839 salts Chemical class 0.000 title claims abstract description 60
- 229930006000 Sucrose Natural products 0.000 title claims abstract description 14
- 239000005720 sucrose Substances 0.000 title claims abstract description 14
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 title claims abstract description 13
- 239000012736 aqueous medium Substances 0.000 title claims description 5
- 238000009472 formulation Methods 0.000 claims abstract description 34
- 239000002537 cosmetic Substances 0.000 claims abstract description 28
- 238000011049 filling Methods 0.000 claims abstract description 12
- 230000037303 wrinkles Effects 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- WEPNHBQBLCNOBB-FZJVNAOYSA-N sucrose octasulfate Chemical compound OS(=O)(=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@H](COS(=O)(=O)O)O[C@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-FZJVNAOYSA-N 0.000 claims description 61
- 229920001282 polysaccharide Polymers 0.000 claims description 29
- 239000005017 polysaccharide Substances 0.000 claims description 29
- 239000000017 hydrogel Substances 0.000 claims description 16
- -1 alkali metal salts Chemical class 0.000 claims description 15
- 238000004132 cross linking Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003963 antioxidant agent Substances 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 9
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 8
- 229960004194 lidocaine Drugs 0.000 claims description 8
- 239000006069 physical mixture Substances 0.000 claims description 7
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000000835 fiber Substances 0.000 claims description 5
- 239000003589 local anesthetic agent Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 4
- 206010013774 Dry eye Diseases 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 229960005015 local anesthetics Drugs 0.000 claims description 4
- 230000003020 moisturizing effect Effects 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 238000005481 NMR spectroscopy Methods 0.000 claims description 3
- 238000000265 homogenisation Methods 0.000 claims description 3
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 claims description 2
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 229960003150 bupivacaine Drugs 0.000 claims description 2
- 238000006073 displacement reaction Methods 0.000 claims description 2
- 230000000887 hydrating effect Effects 0.000 claims description 2
- 229960002409 mepivacaine Drugs 0.000 claims description 2
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 claims description 2
- 229920005862 polyol Polymers 0.000 claims description 2
- 150000003077 polyols Chemical class 0.000 claims description 2
- 229960004919 procaine Drugs 0.000 claims description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960001549 ropivacaine Drugs 0.000 claims description 2
- 150000003378 silver Chemical class 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 48
- XISWAUUBQBEDFB-QRDGSJRXSA-F octapotassium;[(2r,3r,4s,5r,6r)-2-[(2s,3s,4r,5r)-3,4-disulfonatooxy-2,5-bis(sulfonatooxymethyl)oxolan-2-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate Chemical compound [K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[O-]S(=O)(=O)O[C@H]1[C@H](OS([O-])(=O)=O)[C@@H](COS(=O)(=O)[O-])O[C@@]1(COS([O-])(=O)=O)O[C@@H]1[C@H](OS([O-])(=O)=O)[C@@H](OS([O-])(=O)=O)[C@H](OS([O-])(=O)=O)[C@@H](COS([O-])(=O)=O)O1 XISWAUUBQBEDFB-QRDGSJRXSA-F 0.000 description 37
- 239000000243 solution Substances 0.000 description 26
- 239000000499 gel Substances 0.000 description 24
- 102000001974 Hyaluronidases Human genes 0.000 description 21
- 238000012360 testing method Methods 0.000 description 17
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 16
- 229930195725 Mannitol Natural products 0.000 description 16
- 239000000594 mannitol Substances 0.000 description 16
- 235000010355 mannitol Nutrition 0.000 description 16
- 108050009363 Hyaluronidases Proteins 0.000 description 14
- 229960002773 hyaluronidase Drugs 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 150000004804 polysaccharides Chemical class 0.000 description 13
- 230000001954 sterilising effect Effects 0.000 description 12
- 238000004659 sterilization and disinfection Methods 0.000 description 12
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 10
- 229920001287 Chondroitin sulfate Polymers 0.000 description 10
- 230000015556 catabolic process Effects 0.000 description 10
- 229940059329 chondroitin sulfate Drugs 0.000 description 10
- 238000006731 degradation reaction Methods 0.000 description 10
- 229920001542 oligosaccharide Polymers 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 9
- 150000002482 oligosaccharides Chemical class 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 239000008055 phosphate buffer solution Substances 0.000 description 8
- 229920002683 Glycosaminoglycan Polymers 0.000 description 7
- 108010003272 Hyaluronate lyase Proteins 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- 229960000633 dextran sulfate Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- HPILSDOMLLYBQF-UHFFFAOYSA-N 2-[1-(oxiran-2-ylmethoxy)butoxymethyl]oxirane Chemical compound C1OC1COC(CCC)OCC1CO1 HPILSDOMLLYBQF-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000035876 healing Effects 0.000 description 6
- 230000036571 hydration Effects 0.000 description 6
- 238000006703 hydration reaction Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000003431 cross linking reagent Substances 0.000 description 5
- 230000007515 enzymatic degradation Effects 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 238000010525 oxidative degradation reaction Methods 0.000 description 5
- 229910021653 sulphate ion Inorganic materials 0.000 description 5
- 229920002385 Sodium hyaluronate Polymers 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 230000003750 conditioning effect Effects 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000518 rheometry Methods 0.000 description 4
- 229940010747 sodium hyaluronate Drugs 0.000 description 4
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 229920000045 Dermatan sulfate Polymers 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- JULUNWUBCVWBNX-UHFFFAOYSA-A S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+] Chemical compound S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].S(=O)(=O)([O-])[O-].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+].[K+] JULUNWUBCVWBNX-UHFFFAOYSA-A 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 3
- 229940051593 dermatan sulfate Drugs 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 150000002302 glucosamines Chemical class 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 150000002772 monosaccharides Chemical class 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- LFKLPJRVSHJZPL-UHFFFAOYSA-N 1,2:7,8-diepoxyoctane Chemical compound C1OC1CCCCC1CO1 LFKLPJRVSHJZPL-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002971 Heparan sulfate Polymers 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 229920000288 Keratan sulfate Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002225 anti-radical effect Effects 0.000 description 2
- 239000000607 artificial tear Substances 0.000 description 2
- MTDHILKWIRSIHB-QZABAPFNSA-N beta-D-glucosamine 6-sulfate Chemical compound N[C@H]1[C@H](O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O MTDHILKWIRSIHB-QZABAPFNSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- YQYLUTFBYMLTFA-UHFFFAOYSA-A hexadecasodium;octasulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O YQYLUTFBYMLTFA-UHFFFAOYSA-A 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 210000001179 synovial fluid Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- MTDHILKWIRSIHB-UHFFFAOYSA-N (5-azaniumyl-3,4,6-trihydroxyoxan-2-yl)methyl sulfate Chemical compound NC1C(O)OC(COS(O)(=O)=O)C(O)C1O MTDHILKWIRSIHB-UHFFFAOYSA-N 0.000 description 1
- UWFRVQVNYNPBEF-UHFFFAOYSA-N 1-(2,4-dimethylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(C)C=C1C UWFRVQVNYNPBEF-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000052343 Dares Species 0.000 description 1
- ZFIVKAOQEXOYFY-UHFFFAOYSA-N Diepoxybutane Chemical compound C1OC1C1OC1 ZFIVKAOQEXOYFY-UHFFFAOYSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 229940122393 Hyaluronidase inhibitor Drugs 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 235000003805 Musa ABB Group Nutrition 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- WJFVEEAIYIOATH-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine 6-sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O WJFVEEAIYIOATH-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- PRDZVHCOEWJPOB-IVMDWMLBSA-N N-sulfo-D-glucosamine Chemical compound OC[C@H]1OC(O)[C@H](NS(O)(=O)=O)[C@@H](O)[C@@H]1O PRDZVHCOEWJPOB-IVMDWMLBSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000005888 Periodontal Pocket Diseases 0.000 description 1
- 206010034650 Peritoneal adhesions Diseases 0.000 description 1
- 235000015266 Plantago major Nutrition 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- FLUADVWHMHPUCG-OVEXVZGPSA-N Verbascose Natural products O(C[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](OC[C@@H]2[C@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]3(CO)[C@H](O)[C@@H](O)[C@@H](CO)O3)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO[C@@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 FLUADVWHMHPUCG-OVEXVZGPSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 1
- 150000003271 galactooligosaccharides Chemical class 0.000 description 1
- 229960002849 glucosamine sulfate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 201000010041 presbyopia Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- 238000001931 thermography Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002678 vaginoplasty Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- FLUADVWHMHPUCG-SWPIJASHSA-N verbascose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]4[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O4)O)O3)O)O2)O)O1 FLUADVWHMHPUCG-SWPIJASHSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 208000005494 xerophthalmia Diseases 0.000 description 1
- 210000000216 zygoma Anatomy 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
Definitions
- Hyaluronic acid in an aqueous medium, comprising at least one hyaluronic acid and at least one water-soluble salt of sucrose octasulfate
- Hyaluronic acid has been used for more than fifteen years in the field of aesthetics, where it has proved its safety and its efficiency.
- crosslinked hyaluronic acid based gels of biofermental origin are the most used products. Indeed, in the field of aesthetics, non-resorbable implants are less and less used and gels based on other polysaccharides have been abandoned either because of side effects, or because of their animal origin causing a risk of viral contamination.
- hyaluronic acid of biofermental origin in areas such as wrinkle filling, viscosupplementation, ophthalmic treatment or the treatment of urinary incontinence is all the more recognized and appreciated that by its natural presence in the human body, and more particularly in the dermis, the synovial fluid and the cornea, the risks due to side effects are minimized.
- Hyaluronidases are enzymes that degrade hyaluronic acid by catalyzing its hydrolysis to hyaluronic acid oligosaccharides. This degradation has the effect of reducing the viscosity of hyaluronic acid. This decrease in viscosity irreversibly leads to a decrease over time in the desired effects in the fields of wrinkle filling or viscosupplementation, thus bringing injections closer together over time in order to restore their effects, which may cause discomfort or discomfort. pain for the patient.
- a first solution to solve this problem could be to substitute other polysaccharides, less sensitive to hyaluronidases and naturally present in the human body, hyaluronic acid.
- ECM ExtraCellular Matrix
- Chondroitin sulfate, Dermatan sulfate and Keratan sulfate could be interesting.
- chondroitin sulfate is of animal origin and no attempt at synthesis of chondroitin sulfate biofermentaire has, so far, allowed to produce it in amounts compatible with industrial exploitation. It is the same for dermatan sulfate and keratan sulfate, which are available industrially only as products of animal origin.
- compositions comprising in combination with hyaluronic acid, a compound having the inhibitory properties of hyaluronidases.
- the sulphate groups are known in the literature for their anti-oxidant and anti-radical properties, for their high hydration capacity and also for their anti-hyaluronidase action. As regards their antioxidant and anti-radical properties, they protect glycosaminoglycans (GAGs) from depolymerization by reactive oxygen species as described in Moseley R et al. Biochim Biophys Acta., (1995), 1244 (2-3), 245-52. As regards their hydration capacity, it has been demonstrated for example in R. Servaty et al., International Journal of Biological Macromolecules, (2001), 28, 121-127, a greater absorption capacity. water molecules by chondroitin sulfate with respect to hyaluronic acid resulting from the presence of the sulfate group carried by chondroitin sulfate.
- sulphated polysaccharides and more particularly fully O-sulphated glycosaminoglycans are known to exhibit anti-hyaluronidase activity.
- the fully O-sulfated glycosaminoglycans described in this publication are chondroitin sulfate, dermatan sulfate, heparin sulfate, and sulfated hyaluronic acid.
- compositions based on hyaluronic acid for example the patent application WO 03/041724 in the name of Hermida, describes injectable compositions. sterile based on a mixture of sodium hyaluronate and chondroitin sulfate for intraarticular targeting.
- compositions The disadvantage of such compositions remains the animal origin of chondroitin sulfate.
- Dextran sulfate is described as a potent inhibitor of hyaluronidases, and if active doses for a dextran sulfate of 17.7 kDa are Toxic, toxicity increases with molecular weight, and only a few high molecular weight molecules dramatically increase toxicity, as demonstrated by Walton, Br. J. Pharmacol., 1954, 9: 1-14.
- dextran sulfate is described as an anticoagulant used in vivo and in vitro as described for example in US 2715091 and these anticoagulant properties are a priori not compatible with the uses as an ingredient of compositions that are implantable.
- compositions for the treatment of arthritic joints comprising hyaluronic acid and a hyaluronidase inhibitor, such as, for example, a sulphated polysaccharide such as dextran sulfate or sulfate xylose. or heparan sulfate, part of whose components is encapsulated in liposomes to ensure controlled diffusion, but the use of liposomes in compositions intended in particular to be crosslinked seems difficult to envisage.
- This sub-family of mono or sulfated oligosaccharides (formed from 1 to 10 monosaccharides) is interesting because they can be readily available by synthesis, and their carbohydrate structure is nevertheless close to the constituent glycosaminoglycans of the ExtraCellular Matrix, they are very metabolized well while generating non-toxic degradation products.
- sulfated monosaccharides such as sulfated glucosamines, for example glucosamine-3-sulphate described as an inhibitor of cartilage degradation by J.I. Fenton et al. , Osteoarthritis and Cartilage, Volume 8, Issue 6, 2000, 444-451.
- sucrose formed by the condensation of 2 oses, glucose and fructose.
- This sucrose in sulphated form is described as being used as an agent for promoting the healing of wounds by topical application, in solution or in collagenous matrices or on the basis of polyvinyl alcohol in the EP 0 230 023 in the name of Marion Laboratories.
- compositions comprising sucrose octasulfate salts and more particularly examples with the aluminum salt of sucrose octasulfate which is an insoluble salt intended for topical applications. or injections into tissues including joints are described.
- Sucrose octasulfate salts are used more particularly for their healing properties.
- hyaluronic acid can also be used as a healing promoting agent.
- compositions comprising a complex formed between a polysaccharide such as chitosan or hyaluronic acid and a sulfated oligosaccharide such as sucrose octasulfate or one of its salts.
- a polysaccharide such as chitosan or hyaluronic acid
- a sulfated oligosaccharide such as sucrose octasulfate or one of its salts.
- These compositions again, are intended to promote the healing of wounds of tissues comprising collagen such as skin, bones and mucous membranes.
- the formation of the complex is characterized by various techniques such as, for example, MR and infrared spectroscopy, X-ray diffraction, thermography and solubility tests under defined conditions.
- compositions to be implanted or injected implies that they are during their manufacturing process sterilized to meet the minimum health requirements for such compositions.
- the most common sterilization process in the manufacturing processes of such compositions is steam sterilization or autoclaving and a te! process can degrade the products constituting the compositions. It is therefore essential that the rheological, pH metric and biocompatibility properties are preserved and preserved during autoclaving. It is the same with regard to the requirements of injectability through thin needles, which is their main mode of implementation.
- hyaluronic acid gels formulated with the water soluble salts of sucrose octasulfate (SOS) among all possible candidates are the only ones that allow to obtain stable compositions during steam sterilization, otherwise known as autoclaving, and that these moreover have increased remanence due to their resistance to degradation by hyaluronidases, compared to gels comprising hyaluronic acid without water soluble salt of sucrose octasulfate.
- SOS sucrose octasulfate
- the water-soluble salt of sucrose octasulfate has 8 sulfate groups per molecule of sucrose, thus, in the gel formulated with water-soluble salt of sucrose octasulfate the amount of sulfates added per mg of SOS is important.
- the Applicant has also demonstrated as surprisingly, that the addition of water-soluble salt of sucrose octasulfate in hyaluronic acid-based gels does not cause a drop in viscosity or elasticity of the gel during sterilization.
- the Applicant proposes to solve the problem of hyaluronidase degradation of compositions comprising hyaluronic acid by the addition of a water soluble salt of sucrose octasulfate, while retaining the ability of these compositions to be used in the field of wrinkle filling, viscosupplementation, cosmetic or pharmaceutical formulations due to the stability of their rheological properties during the steam sterilization phase during the manufacturing process.
- the present invention solves all the problems mentioned above and further allows to obtain compositions according to the invention retaining their rheological properties during autoclaving and having a higher remanence (half-life time). higher) compared to the compositions of the prior art.
- the present invention relates to a sterilized composition
- a sterilized composition comprising at least one hyaluronic acid, crosslinked or non-crosslinked, or one of its salts, and at least one water-soluble salt of sucrose octasulfate, the processes for producing said composition and also the use of said composition for the formulation of a viscosupplementation composition or for the formulation of a composition for filling wrinkles, for the formulation of a cosmetic composition or for the formulation of a pharmaceutical composition.
- the composition according to the present invention has hyaluronidase resistance properties and is characterized by rheological properties preserved after steam sterilization and at least similar to those of a composition comprising only at least one hyaluronic acid, crosslinked or uncrosslinked, or one of its salts.
- the current The invention also relates to a cosmetic formulation comprising the composition according to the invention and at least one cosmetically acceptable excipient.
- the present invention makes it possible to obtain hyaluronidase-resistant compositions that meet the requirements for autoclaving stability of the compositions intended for the aforementioned domains.
- the present invention relates to a composition, in aqueous medium, comprising at least one hyaluronic acid and at least one water-soluble salt of sucrose octasulfate, characterized in that said composition is a physical mixture and in that the mass ratio between the content in hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [SOS] is greater than or equal to 0.1.
- hyaluronic acid hyaluronic acid, crosslinked or uncrosslinked, alone or in mixture, optionally chemically modified by substitution, alone or in mixture, optionally in the form of one of its salts, alone or in admixture .
- the composition according to the invention comprises at least one non-crosslinked hyaluronic acid or one of its salts, alone or in admixture.
- the composition according to the invention comprises at least one crosslinked hyaluronic acid or one of its salts, alone or in admixture.
- the composition according to the invention comprises at least one co-crosslinked hyaluronic acid or one of its salts, alone or in admixture.
- the composition according to the invention comprises at least one cross-linked or non-cross-linked, chemically modified hyaluronic acid, or one of its salts, alone or as a mixture.
- the hyaluronic acid is in the form of sodium or potassium salt.
- the composition according to the invention is characterized in that the water-soluble salt of sucrose octasulfate is chosen from the group consisting of alkali metal salts, metal salts and alkaline earth metals, silver salts, ammonium salts, amino acid salts.
- the composition according to the invention is characterized in that the water-soluble salt of sucrose octa sulfate is selected from the group consisting of alkali metal salts or alkaline earth metal salts.
- the composition according to the invention is characterized in that the water-soluble salt of sucrose octasulfate is the sodium salt of sucrose octasulfate or the potassium salt of sucrose octasulfate.
- the composition according to the invention is characterized in that the water-soluble salt of sucrose octasulfate is the sodium salt of sucrose octasulfate.
- the composition according to the invention is characterized in that the water-soluble salt of sucrose octasulfate is the potassium salt of sucrose octasulfate.
- the maximum solubility of the potassium salt of sucrose octasulfate is 40 mg / g, so the ratio [HA] / [SOS] minimum in the compositions of the present invention is 0, 1, since the minimum concentration HA acceptable in the compositions of the present invention is 4 mg / g in order to obtain adequate consistency with the uses of the present invention. Since the solubility of the sodium salt of sucrose octasulfate is greater than that of the potassium salt, the solubility limit of the potassium salt of sucrose octasulfate was taken into account in determining the minimum value of the [HA] / [SOS] ratio.
- aqueous medium a composition in the form of an aqueous solution, optionally in the presence of soluble salt or buffer, optionally in the form of a gel or hydrogel.
- physicochemicals that can be characterized by different analytical methods.
- the Applicant has chosen to characterize the physical mixture nuclear magnetic resonance spectroscopy (RMIM).
- RMIM physical mixture nuclear magnetic resonance spectroscopy
- the NMR spectrum of the mixture according to the invention is a spectrum 1D proton 1 H.
- the NMR spectrum of a physical mixture comprising a water-soluble salt of sucrose octasulfate is characterized in that the values of the chemical shifts of the protons of the water-soluble salt of sucrose octasulfate in solution, alone, are equal to the values of the chemical shifts of the protons of the water-soluble salt of sucrose octasulfate in the physical mixture according to the invention, which proves that there is no interaction or reaction between the water-soluble salt of sucrose octasulfate and hyaluronic acid.
- sucrose octasulfate is identical to the value of the chemical shift of the anomeric proton salt sucrose octasulfate alone in solution.
- the composition according to the invention is characterized in that the mass ratio between the content of hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is between 0.1 and 5000.
- the composition according to the invention is characterized in that the mass ratio between the content of hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is between 0.1 and 2500.
- the composition according to the invention is characterized in that the mass ratio between the content of hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is between 1 and 1000.
- the composition according to the invention is characterized in that the mass ratio between the hyaluronic acid content [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is between 10 and 500.
- the composition according to the invention is characterized in that the mass ratio between the content of hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is between 0.1 and 100.
- the composition according to the invention is characterized in that the mass ratio between the acid content hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [SOS] is between 0.5 and 50.
- the composition according to the invention is characterized in that the mass ratio between the content of hyaluronic acid [HA] and the water-soluble salt content of sucrose octasulfate [SOS], [HA] / [ SOS] is equal to 20.
- the composition according to the invention is characterized in that the water-soluble salt content of sucrose octasulfate is between 0.01 mg / g and 40 mg / g of composition.
- the composition according to the invention is characterized in that the water-soluble salt content of sucrose octasulfate is between 0.1 mg / g and 10 mg / g of composition.
- the composition according to the invention is characterized in that the water-soluble salt content of sucrose octasulfate is between 0.1 mg / g and 1 mg / g of composition. In one embodiment, the composition according to the invention is characterized in that the hyaluronic acid content is between 2 mg / g and 50 mg / g of composition.
- the composition according to the invention is characterized in that the hyaluronic acid content is between 4 mg / g and 40 mg / g of composition.
- the composition according to the invention is characterized in that the hyaluronic acid content is between 10 mg / g and 30 mg / g of composition.
- the composition according to the invention is characterized in that it comprises at least one non-crosslinked hyaluronic acid.
- the composition according to the invention is characterized in that it comprises at least one crosslinked hyaluronic acid.
- the degree of crosslinking X is defined as being equal to the ratio: (Number of moles of crosslinking agent introduced into the reaction medium)
- the crosslinked hyaluronic acid has a degree of crosslinking X of between 0.001 and 0.5.
- the crosslinked hyaluronic acid has a degree of crosslinking X of between 0.01 and 0.25.
- the crosslinked hyaluronic acid has a degree of crosslinking X of between 0.1 and 0.2.
- the hyaluronic acid is co-crosslinked as described in application WO 2000/0046253 in the name of Fermentech or WO 2004/092222 in the name of Cornéal or even FR2865737 in the name of ANTEIS.
- the composition according to the invention is characterized in that it comprises a mixture of crosslinked and non-crosslinked hyaluronic acids as described in the application WO2005061611 in the name of Innomed Ltd.
- the composition according to the invention is characterized in that it comprises a mixture of crosslinked hyaluronic acids.
- the mixture of crosslinked hyaluronic acids is a monophasic mixture such as that described in the patent application WO 2009/071697 in the name of the Applicant.
- the composition according to the invention is characterized in that it comprises at least one hyaluronic acid substituted with a group providing lipophilic or moisturizing properties, such as, for example, the substituted hyaluronic acids as described in US Pat. the application WO2013079889 in the name of the applicant.
- the composition further comprises another polysaccharide.
- this other polysaccharide is chosen from the group consisting of cellulose, alginic acid or one of their salts.
- Mw or "molecular weight” is the mass-average molecular weight of the polymers, measured in Daltons.
- the composition according to the invention is characterized in that the molecular weight Mw of hyaluronic acid is in a range of 0.01 MDa and 5 MDa.
- the composition according to the invention is characterized in that the molecular weight Mw of hyaluronic acid is in a range of 0.1 MDa and 3.5 MDa. In one embodiment, the composition according to the invention is characterized in that it comprises, in addition, at least one active ingredient.
- composition according to the invention is characterized in that the active ingredient is selected from antioxidants, local anesthetics, vitamins, alone or in combination.
- composition according to the invention is characterized in that the antioxidants are chosen from polyols.
- composition according to the invention is characterized in that the antioxidants are chosen from mannitol and sorbitol, alone or in combination.
- composition according to the invention is characterized in that the antioxidant is mannitoi.
- composition according to the invention is characterized in that the antioxidant agent is sorbitol.
- the composition according to the invention is characterized in that the antioxidant is a combination of mannitol and sorbitol.
- the composition according to the invention is characterized in that the local anesthetics are chosen from the group consisting of lidocaine, procaine, mepivacaine, ropivacaine and bupivacaine, and their pharmaceutically acceptable salts. .
- composition according to the invention is characterized in that the local anesthetic is lidocaine hydrochloride.
- the composition according to the invention is characterized in that the content of active principle (s) is between 0.01 and 10% by weight relative to the total weight of the composition. . In one embodiment, the composition according to the invention is characterized in that the content of active principle (s) is between 0, 1 and 5% by weight relative to the total weight of the composition. . In one embodiment, the composition according to the invention is characterized in that it is stable to sterilization by steam autoclaving.
- the invention is a viscosupplementation composition characterized in that it comprises at least one composition according to the invention.
- the invention is a composition for the treatment of xerophthalmia or dry eye, characterized in that it comprises at least one composition according to the invention.
- said compositions are used as artificial tears, lacrimal gels or lubricants.
- the invention is a cosmetic formulation characterized in that it comprises a composition according to the invention and at least one cosmetically acceptable excipient.
- the cosmetic formulation according to the invention is characterized in that it comprises between 0.01 and 10% by weight of a composition according to the invention relative to the total weight of said cosmetic formulation. .
- the cosmetic formulation according to the invention is characterized in that the at least one cosmetically acceptable excipient is selected from conventional cosmetic adjuvants.
- cosmetic adjuvants are meant excipients chosen in particular from fatty substances, organic solvents, ionic or nonionic thickeners, softeners, antioxidants, opacifiers, stabilizers, emollients and silicones. - hydroxyacids, defoamers, moisturizers, fragrances, preservatives, surfactants, fillers, sequestering agents, polymers, propellants, alkalizing or acidifying agents, dyes, or any other ingredient normally used in cosmetic.
- the cosmetic formulation according to the invention may furthermore comprise other active agents, in particular moisturizing, humectant, soothing, anti-inflammatory and cicatrizing agents.
- the cosmetic formulations according to the invention can be prepared according to the techniques well known to those skilled in the art, in particular those intended for the preparation of oil-in-water (O / W) or water-in-water type emulsions. Oil (E / H).
- This cosmetic formulation may be in particular in the form of an emulsion, simple or complex (O / W, W / O, O / W / H or W / O / W) such as cream, milk, a gel or a cream gel, powder, solid stick and optionally be packaged in aerosol and be in the form of foam or spray.
- the cosmetic formulation is sterilized according to the techniques well known to those skilled in the art, and in particular by gamma irradiation.
- the present invention also relates to a cosmetic formulation according to the invention characterized in that it is administrable topically in the form of lotion, cream, oil, stick, shampoo or any other suitable forms.
- the cosmetic, dermatological or pharmaceutical formulation according to the invention can be used as a protective composition of the human epidermis against the aggressions of the external elements and thus fight against the premature aging of the epidermis.
- the invention also relates to a method for manufacturing a composition according to the invention.
- the method according to the invention is characterized in that it comprises at least:
- a homogenization step and A step of autoclaving with steam.
- the method according to the invention is characterized in that the hydration step is carried out at room temperature.
- the method according to the invention is characterized in that the homogenization step is carried out at ambient temperature. In one embodiment, the method according to the invention is characterized in that the steam autoclaving step is carried out at a temperature of 121 to 134 ° C, for a time adapted to the temperature.
- the method according to the invention is characterized in that it further comprises at least one step of conditioning the homogenized mixture in syringes.
- the method according to the invention is characterized in that it further comprises at least one step of conditioning the homogenized mixture in single-dose vials.
- the method according to the invention is characterized in that it further comprises at least one crosslinking step.
- the method according to the invention is characterized in that the crosslinking step is between the hydration step and the mixing step. In one embodiment, the method according to the invention is characterized in that it comprises a step of mixing two hyaluronic acids previously crosslinked as in the method described in WO2013 / 079889. In one embodiment, the process according to the invention is characterized in that the crosslinking step is carried out using at least one crosslinking agent. In one embodiment, the method according to the invention is characterized in that the crosslinking agent is bi- or polyfunctional.
- the process according to the invention is characterized in that the bi- or polyfunctional crosslinking agent is chosen from the group consisting of ethyleneglycoldiglycidyl ether and butanedioldiglycidyl ether (BDDE).
- the bi- or polyfunctional crosslinking agent is chosen from the group consisting of ethyleneglycoldiglycidyl ether and butanedioldiglycidyl ether (BDDE).
- polyglycerol polyglycidyl ether polyethyleneglycoldiglycidyl ether, polypropyleneglycoldiglycidyl ether, a bis- or polyepoxy such as 1,2,3,4-diepoxybutane or 1,2,7,8-diepoxyoctane, a dialkylsulfone, divinylsulfone, formaldehyde, epichlorohydrin or even glutaraldehyde, carbodiimides such as, for example, 1-ethyl-3- [3-dimethylaminopropyl] carbodiimide hydrochloride (EDC).
- EDC 1-ethyl-3- [3-dimethylaminopropyl] carbodiimide hydrochloride
- the process according to the invention is characterized in that the bifunctional crosslinking agent is butanedioldiglycidyl ether (BDDE) or 1,2,7,8-diepoxyoctane.
- BDDE butanedioldiglycidyl ether
- 1,2,7,8-diepoxyoctane 1,2,7,8-diepoxyoctane
- the manufacturing method according to the invention is characterized in that the crosslinking step is carried out according to the techniques known to those skilled in the art.
- the method according to the invention is characterized in that it comprises, after the crosslinking step, at least one purification and washing step carried out according to the techniques known to man of the job.
- the invention relates to the use of a composition according to the invention for the formulation of a viscosupplementation composition.
- the invention relates to the use of a composition according to the invention for the formulation of a composition for filling wrinkles.
- the targeted applications are more particularly the commonly used applications in the context of injectable viscoelastics and polysaccharides used or potentially usable in the following pathologies or treatments:
- the hydrogel obtained according to the method of the invention may be used:
- fine diameter needles 27 Gauge for example
- composition according to the invention also finds an important application in joint surgery and dental surgery for filling periodontal pockets, for example.
- composition according to the present invention being more widely intended to: fill volumes;
- the invention also relates to a kit comprising a composition according to the invention, packaged in syringes and sterilized after conditioning.
- the invention also relates to a kit comprising a composition according to the invention, packaged in single dose vials and sterilized after conditioning.
- the composition according to the invention also has an application in the cosmetic or pharmaceutical field.
- composition according to the invention will be used as moisturizing active ingredient in a cosmetic composition.
- composition according to the invention will be used as hydration composition of eyes with dry eye, namely as artificial tear.
- compositions may further comprise any cosmetically or pharmaceutically acceptable ingredient.
- composition according to the present invention as well as its manufacturing processes and their properties are illustrated in the examples below.
- composition according to the invention comprising non-crosslinked hyaluronic acid and potassium sucrose octasulfate.
- NaHA Sodium hyaluronate
- the uncrosslinked NaHA hydrogel thus obtained at a concentration of about 30 mg / g in NaHA.
- KSOS potassium sucrose octasulfate
- a phosphate buffer solution (19.94 g)
- the NaHA hydrogel obtained in the preceding step is diluted by addition of the aqueous potassium sucrose octasulfate solution previously prepared. The composition thus obtained is then homogenized.
- composition comprising non-crosslinked NaHA at a concentration of 20 mg / g and KSOS at a concentration of
- Example 2 [000145] This example illustrates an exemplary composition according to the invention comprising crosslinked hyaluronic acid and potassium sucrose octasulfate.
- composition comprising crosslinked hyaluronic acid is obtained according to the crosslinking procedure described in WO 2009/071697 (Example 1, first part) in the name of VI ACY from sodium hyaluronate (NaHA) fibers ( 1 g, molecular weight: about 2.7 MDa) and butanedioldiglycidyl ether (BDDE) (54 mg).
- the composition thus obtained has a concentration of about 30 mg / g of cross-linked NaHA with an X-crosslinking rate of about 0.12.
- the crosslinked NaHA hydrogel obtained in the previous step is diluted in the aqueous potassium sucrose octasulfate solution previously prepared.
- the composition thus obtained is then homogenized.
- a composition comprising cross-linked NaHA at a concentration of 20 mg / g and sucrose octasulfate of potassium at a concentration of 1 mg / g; the mass ratio [HA] / [SOS] is therefore 20.
- This example illustrates an example of a composition according to the invention comprising non-crosslinked hyaluronic acid, potassium sucrose octasulfate and mannitol.
- composition comprising non-crosslinked hyaluronic acid and potassium sucrose octasulfate is prepared according to the procedure of Example 1, from a hyaluronic acid hydrogel at a concentration of 30 mg / g and potassium sucrose octasulfate solution at a concentration of 10 mg / g.
- composition obtained above comprises non-crosslinked hyaluronic acid at a concentration of 20 mg / g, mannitol at a concentration of 20 mg / g and potassium sucrose octasulfate at a concentration of 1 mg / g; the mass ratio [HA] / [SOS] is therefore 20.
- This example illustrates an example of a composition according to the invention comprising crosslinked hyaluronic acid, potassium sucrose octasulfate and mannitol.
- a composition comprising crosslinked NaHA is prepared according to the procedure described in Example 2 from a NaHA hydrogel at a concentration of 30 mg / g and potassium sucrose octasulfate at a concentration of 10 mg / ml. boy Wut.
- composition thus obtained comprises crosslinked hyaluronic acid at a concentration of 20 mg / g, mannitol at a concentration of 20 mg / g and potassium sucrose octasulfate at a concentration of 1 mg / g; the mass ratio [HA] / [SOS] is therefore 20.
- This example illustrates an example of a composition according to the invention comprising non-crosslinked hyaluronic acid, potassium sucrose octasulfate and lidocaine.
- the composition comprising non-crosslinked hyaluronic acid and potassium sucrose octasulfate is prepared according to the procedure of Example 1, from a hyaluronic acid hydrogel at a concentration of 30 mg / g and potassium sucrose octasulfate solution at a concentration of 10 mg / g.
- a lidocaine solution at a concentration of 13 mg / g is carried out according to the procedure described in WO 2009/024670 in the name of ANTEIS or according to the procedure described in US Pat. US applications 61 / 791,977 or FR 13/52971 in the name of VIVACY.
- the composition thus obtained comprises uncrosslinked hyaluronic acid at a concentration of 20 mg / g, lidocaine at a concentration of 3 mg / g and potassium sucrose octasulfate at a concentration of 1 mg / g; the mass ratio [HA] / [SOS] is therefore 20.
- This example illustrates an example of a composition according to the invention comprising crosslinked hyaluronic acid, potassium sucrose octasulfate and lidocaine.
- a composition comprising crosslinked NaHA is prepared according to the procedure described in Example 2 from a NaHA hydrogel at a concentration of 30 mg / g and potassium sucrose octasulfate at a concentration of 10 mg / ml. boy Wut.
- the addition of a solution of lidocaine at a concentration of 13 mg / g to the composition obtained above is carried out according to the procedure described in WO 2009/024670 in the name of ANTEIS or according to the procedure described in US Pat. US 61 / 791,977 or FR 13/52971 in the name of VI ACY.
- the composition thus obtained comprises crosslinked hyaluronic acid at a concentration of 20 mg / g, lidocaine at a concentration of 3 mg / g and potassium sucrose octasulfate at a concentration of 1 mg / g; the mass ratio [HA] / [SOS] is therefore 20.
- composition according to the invention comprising non-crosslinked hyaluronic acid and potassium sucrose octasulfate for the treatment of dry eye.
- NaHA Sodium hyaluronate
- the uncrosslinked NaHA hydrogel thus obtained has a concentration of about 6 mg / g in NaHA.
- KSOS Sucrose potassium octasulfate
- the NaHA hydrogel obtained in the preceding step is diluted by addition of the aqueous potassium sucrose octasulfate solution previously prepared. The composition thus obtained is then homogenized.
- composition comprising non-crosslinked NaHA at a concentration of 4 mg / g and KSOS at a concentration of 10 mg / g is obtained; the mass ratio [HA] / [SOS] is therefore 0.4. [000179]
- the composition thus obtained is packaged in single-dose vials, which are sterilized.
- This example illustrates a cosmetic formulation. Cetearyl alcohol 5%
- esters (dicaprylic ether, myristyl myristate) 10%
- Non-crosslinked hyaluronic acid composition sucrose octasulfate of 1% potassium obtained in Example 1 ⁇ cerine 5%
- Non-crosslinked hyaluronic acid composition sucrose octasulfate of 1% potassium obtained according to Example 1 with a ratio [HA] / [SOS] of 4
- Citric acid 0, 1%
- the cosmetic formulation is sterilized by gamma irradiation at doses of 5-25 kGy and preferably 7-15 kGy.
- the viscosity ⁇ of the sterilized compositions after the steam autoclaving step is characterized on a TA Instruments AR 2000 Ex rheometer, under a constraint imposed on 25 ° C. The viscosity value is read at a stress of 0.02 s -1 .
- the percentage of loss of viscosity is the value of the difference in the viscosity of the reference composition after steam autoclaving and the viscosity of the composition comprising non-crosslinked hyaluronic acid and an oligo-polysaccharide or sulfated ose after steam autoclaving on the value of the viscosity of the reference composition after steam autoclaving.
- the elastic component G 'of the compositions sterilized after the autoclaving step is characterized on TA Instruments AR 2000 Ex rheometer, in oscillation at 25 ° C., the values of the elastic component being recorded at a frequency of 1 Hz.
- the percentage of loss of the elastic component G ' is the value of the difference of the elastic component G' of the reference composition after steam autoclaving and the elastic component G 'of the composition comprising crosslinked hyaluronic acid and oligopolysaccharide or sulfated ose after steam autoclaving on the value of the elastic component G' of the reference composition after steam autoclaving.
- a reference composition is formulated, replacing the aqueous oligosaccharide or sulfated osé solution with the same amount of aqueous phosphate buffer solution.
- a) Stability in steam autoclaving of compositions comprising non-crosslinked hyaluronic acid and a sulfated oligo-polysaccharide or a sulfated ose [000188] Nine compositions comprising non-crosslinked hyaluronic acid and a sulfated oligo-polysaccharide or sulphate ose at a concentration of 1 mg / g in the composition are prepared according to the procedure described in Example 1.
- a reference composition is also formulated, replacing the aqueous solution oligo-polysaccharide or sulfated osé by the same amount of aqueous phosphate buffer solution.
- compositions comprising non-crosslinked hyaluronic acid and a sulfated oligo-polysaccharide or sulfated ose at a concentration of 1 mg / g relative to the composition of reference
- compositions comprising non-crosslinked hyaluronic acid, sulfated oligo-polysaccharide or sulfated ose and mannitol
- a series of five compositions comprising non-crosslinked hyaluronic acid, mannitol and a sulphated oligo-polysaccharide or sulphate ose at a concentration of 1 mg / g in the composition is prepared according to the procedure described in Example 3.
- a reference composition is also formulated, replacing the aqueous solution of oligo-polysaccharide or sulfated osé by the same amount of aqueous phosphate buffer solution.
- the percentages of loss of the viscosity of the compositions according to the procedure of Example 3 relative to the reference composition are measured and the results obtained are shown in Table 2 below:
- compositions comprising non-crosslinked hyaluronic acid, mannitol and a sulfated oligo-polysaccharide or sulfated ose at a concentration of 1 mg / g relative to the reference composition
- compositions comprising non-crosslinked hyaluronic acid, mannitol and a glucosamine sulfate, there is a loss of viscosity with respect to the reference composition.
- compositions for which no loss of viscosity is observed after steam autoclaving with respect to the reference composition are compositions comprising a water-soluble salt of sucrose octasulfate.
- compositions comprising cross-linked hyaluronic acid, sulfated oligo-polysaccharide or sulfated ose and mannitol
- compositions comprising crosslinked hyaluronic acid, mannitol and a sulfated oligo-polysaccharide or a sulfated ose at a concentration of 1 mg / g in the composition is prepared according to the procedure described in the example 4.
- a reference composition is also formulated, replacing the aqueous solution of oligo-polysaccharide or sulfated osé with an equivalent amount of aqueous phosphate buffer solution.
- the percentages of loss of the elastic component G 'of the compositions according to the procedure of Example 4 with respect to the reference composition are measured and the results obtained are shown in Table 3 below:
- Percent loss of the elastic component G after the step of steam autoclaving compositions comprising crosslinked hyaluronic acid, mannitol, and a sulfated oligo-polysaccharide or sulfated ose at a concentration of 1 mg / g compared to the reference composition
- compositions comprising potassium sucrose octasulfate that there is no loss of the G 'component after steam autoclaving with respect to the reference composition.
- G 'component after steam autoclaving with respect to the reference composition.
- This observation is the same as the hyaluronic acid is or not crosslinked and the compositions include or not mannitol.
- the analyzes in solution are carried out on a Bruker Avance spectrometer operating at 600 MHz (1H) and equipped with a TCI probe (cryoprobe).
- FIG. 1 is the 1H NMR spectrum of potassium sucrose octasulfate alone in solution in water.
- FIG. 2 is a superposition of the 1H RM spectra of the composition of Example 4 before and after sterilization.
- the degradation test was developed on the basis of the test described in the publication "Comparison of the sensitivity of 11 crosslinked hyaluronic acid gels to bovine testis hyaluronidase", I. Sali, G. Ferard, Polymer Deg. and Stability, (2007), 92, 915-919 and the patent application WO 2009/068215.
- composition A a composition prepared according to the procedure of Example 2 comprising cross-linked NaHA at a concentration of 20 mg / g and potassium sucrose octasulfate at a concentration of 3 mg / g. in NaCl buffer (Composition A) and on the composition of Example 4 (Composition B), sterilized by steam autoclaving and also sterilized reference compositions by steam autoclaving.
- the reference composition A and the reference composition B are formulated by replacing the aqueous potassium sucrose octasulfate solution with the same amount of aqueous phosphate buffer solution.
- compositions were subjected to an enzymatic degradation test in vitro at 37 ° C. This test makes it possible to simulate the subsequent in vivo remanence of the injected compositions.
- compositions are degraded by hyaluronidases, by mixing the compositions to be tested with a hyaluronidase solution.
- the degradation is followed by rheology at 37 ° C. (on TA Instruments AR 2000 Ex rheometer), by measuring the complex viscosity.
- compositions A and B, sterilized by steam autoclaving have half-life times greater than those of the reference compositions, sterilized by steam autoclaving under the same conditions; in fact compositions A and B, sterilized by steam autoclaving respectively have 24% and 43% higher remanence vis-à-vis enzymatic degradation compared to reference compositions A and B sterilized by steam autoclaving.
- the oxidative degradation tests were carried out on the composition of Example 4, sterilized by steam autoclaving and on a reference composition also sterilized by steam autoclaving under the same conditions.
- the reference composition is formulated, replacing the aqueous potassium sucrose octasulfate solution with the same amount of aqueous phosphate buffer solution.
- the compositions were subjected to an in vitro oxidative degradation test at 45.degree. This test makes it possible to simulate the subsequent in vivo remanence of the injected compositions.
- compositions are degraded in the presence of hydrogen peroxide.
- the degradation is followed by rheology at 45 ° C. (on TA Instruments AR 2000 Ex rheometer), by measuring the complex viscosity.
- Example 4 Oxidative degradation tests on a composition of Example 4, sterilized by steam autoclaving and on a reference composition based on crosslinked hyaluronic acid, sterilized by steam autoclaving [000220]
- the composition of Example 4, sterilized by steam autoclaving has a half-life longer than that of the reference composition sterilized by steam autoclaving under the same conditions; indeed, the composition of Example 4, sterilized by steam autoclaving has a greater remanence of 30% vis-à-vis the oxidative degradation relative to the reference composition, sterilized by steam autoclaving.
- the percentage loss of the elastic component G 'with respect to the reference composition is measured according to Example 8 and the difference between the injectability force, through hypodermic needles 30 Gauge 1/2, the gel reference and gels comprising potassium sucrose octasulfate is measured.
- Percentage loss of the elastic component G after the steam autoclaving step of compositions comprising cross-linked hyaluronic acid in the presence of varying concentrations of potassium sucrose octasulfate.
- the gels are prepared according to the procedure described in Example 2 and then characterized by rheology according to Example 8.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Birds (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Inorganic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL13733396T PL2861301T3 (en) | 2012-06-13 | 2013-06-13 | Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble salt |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261659140P | 2012-06-13 | 2012-06-13 | |
FR1255543A FR2991876B1 (en) | 2012-06-13 | 2012-06-13 | COMPOSITION, IN AQUEOUS MEDIUM, COMPRISING AT LEAST ONE HYALURONIC ACID AND AT LEAST ONE WATER-SOLUBLE SALT OF SUCROSE OCTASULFATE |
PCT/FR2013/051380 WO2013186493A2 (en) | 2012-06-13 | 2013-06-13 | Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble salt |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2861301A2 true EP2861301A2 (en) | 2015-04-22 |
EP2861301B1 EP2861301B1 (en) | 2019-02-20 |
Family
ID=46785648
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP13733396.9A Active EP2861301B1 (en) | 2012-06-13 | 2013-06-13 | Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble salt |
Country Status (17)
Country | Link |
---|---|
US (1) | US9314530B2 (en) |
EP (1) | EP2861301B1 (en) |
JP (1) | JP6178414B2 (en) |
KR (1) | KR20150023468A (en) |
CN (1) | CN104394934B (en) |
AU (1) | AU2013276343B2 (en) |
BR (1) | BR112014029510A2 (en) |
CA (1) | CA2876057A1 (en) |
EA (1) | EA201492208A1 (en) |
ES (1) | ES2728686T3 (en) |
FR (1) | FR2991876B1 (en) |
IL (1) | IL235776A0 (en) |
MX (1) | MX354544B (en) |
PL (1) | PL2861301T3 (en) |
SG (1) | SG11201407857SA (en) |
TR (1) | TR201907427T4 (en) |
WO (1) | WO2013186493A2 (en) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9492474B2 (en) | 2013-07-10 | 2016-11-15 | Matrix Biology Institute | Compositions of hyaluronan with high elasticity and uses thereof |
US9421198B2 (en) | 2013-07-30 | 2016-08-23 | Teoxane | Composition comprising hyaluronic acid and mepivacaine |
FR3015290B1 (en) * | 2013-12-23 | 2017-01-13 | Lab Vivacy | HYALURONIC ACID COMPOSITIONS COMPRISING MEPIVACAINE |
CN106659663A (en) * | 2014-06-30 | 2017-05-10 | 纽璀克斯技术公司 | Combination products and cosmetic compositions for controlling skin disorders and skin aging that affect keratinocytes and/or fibroblasts and the dermis |
FR3032617B1 (en) * | 2015-02-16 | 2018-03-16 | Kylane Laboratoires Sa | PROCESS FOR THE PREPARATION OF AN INJECTABLE HYDROGEL; HYDROGEL OBTAINED; USE OF THE HYDROGEL OBTAINED |
US10004824B2 (en) | 2015-05-11 | 2018-06-26 | Laboratoires Vivacy | Compositions comprising at least one polyol and at least one anesthetic |
FR3036035B1 (en) | 2015-05-11 | 2018-10-05 | Laboratoires Vivacy | COMPOSITIONS COMPRISING AT LEAST ONE POLYOL AND AT LEAST ONE ANESTHETIC |
CN104926889A (en) * | 2015-05-24 | 2015-09-23 | 广西师范学院 | Sucrose sulfate copper and silver compound as well as preparation method and application thereof |
RU2020123728A (en) | 2015-09-24 | 2021-01-18 | Матрикс Байолэджи Инститьют | COMPOSITIONS OF HYALURONIC ACID WITH HIGH ELASTIC PROPERTIES AND METHODS OF THEIR APPLICATION |
FR3044557B1 (en) * | 2015-12-07 | 2017-12-01 | Benedicte Vincente Gavard Molliard Tauzin | NOVEL COMPOSITION INJECTABLE; PROCESS FOR THE PREPARATION OF SAID COMPOSITION; USE OF SAID COMPOSITION |
WO2017102001A1 (en) | 2015-12-16 | 2017-06-22 | Vplus International Sa | Hyaluronic acid composition for penile injections |
FR3047666A1 (en) * | 2016-02-15 | 2017-08-18 | Benedicte Vincente Gavard Molliard Tauzin | INJECTABLE COMPOSITION; PROCESS FOR THE PREPARATION OF SAID COMPOSITION; USE OF SAID COMPOSITION |
FR3058064B1 (en) | 2016-10-28 | 2020-08-07 | Lab Vivacy | COMPOSITION BASED ON HYALURONIC ACID INCLUDING MEPIVACAINE |
JP2020503377A (en) | 2016-12-13 | 2020-01-30 | ベータ セラピューティクス プロプライアタリー リミティド | Heparanase inhibitors and uses thereof |
US11787783B2 (en) | 2016-12-13 | 2023-10-17 | Beta Therapeutics Pty Ltd | Heparanase inhibitors and use thereof |
EP3554505A4 (en) * | 2016-12-13 | 2020-09-16 | Beta Therapeutics Pty. Ltd. | Methods of treating ocular disorders |
FR3109153B1 (en) | 2020-04-10 | 2022-07-15 | Teoxane SA | Compositions based on at least two glycosaminoglycans |
KR102664134B1 (en) * | 2023-11-23 | 2024-05-10 | 한국콜마주식회사 | Cosmetic composition with hyaluronic acid and derivatives thereof |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2715091A (en) | 1949-11-28 | 1955-08-09 | Nat Res Dev | Dextran sulfate as anticoagulant, process of preparing same, and sterile solution thereof |
AU607690B2 (en) | 1985-12-24 | 1991-03-14 | Marion Laboratories, Inc. | Use of synthetic sulfated saccharides to enhance wound healing |
US5916880A (en) | 1987-12-21 | 1999-06-29 | Bukh Meditec A/S | Reduction of skin wrinkling using sulphated sugars |
DK505488D0 (en) | 1987-12-21 | 1988-09-09 | Bar Shalom Daniel | MEDIUM AND USE OF SAME |
DK86492D0 (en) | 1992-06-30 | 1992-06-30 | Bukh Meditec | PHARMACEUTICAL PRODUCT |
WO1998022114A1 (en) | 1996-11-15 | 1998-05-28 | Dumex-Alpharma A/S | A method for promoting tissue repair |
JP2000178196A (en) * | 1998-12-11 | 2000-06-27 | Seikagaku Kogyo Co Ltd | Novel hyaluronidase inhibitor and preparation for external use |
GB9902412D0 (en) | 1999-02-03 | 1999-03-24 | Fermentech Med Ltd | Process |
CA2451248A1 (en) * | 2001-06-25 | 2003-01-03 | Depuy International Limited | Composition comprising glycosaminoglycans and hyaluronidase inhibitors for the treatment of arthritic joints |
US20050187150A1 (en) * | 2001-10-31 | 2005-08-25 | New York University | Structure-based design and synthesis of FGF inhibitors and FGF modulator compounds |
MXPA01011542A (en) | 2001-11-13 | 2003-05-22 | Alcon Inc | Regeneration of articular cartilage damaged by osteoarthritis i and ii, by means of intra-articular application of sodium hyaluronate and chondroitin sulphate in a gel carrier. |
AUPS052802A0 (en) | 2002-02-15 | 2002-03-07 | Praxis Pharmaceuticals International Pty Ltd | Carbohydrate-based anti-wrinkle and tissue remodelling compounds |
US20080003258A1 (en) | 2002-10-16 | 2008-01-03 | Marcum Frank D | Composition and Method for Treating Rheumatoid Arthritis |
ES2374157T3 (en) | 2002-10-16 | 2012-02-14 | Arthrodynamic Technologies, Animal Health Division, Inc. | TREATMENT FOR TRAUMATIC SYNOVITIS AND DAMAGED ARTICULAR CARTRIDGE. |
FR2861734B1 (en) | 2003-04-10 | 2006-04-14 | Corneal Ind | CROSSLINKING OF LOW AND HIGH MOLECULAR MASS POLYSACCHARIDES; PREPARATION OF INJECTABLE SINGLE PHASE HYDROGELS; POLYSACCHARIDES AND HYDROGELS OBTAINED |
GB0329907D0 (en) | 2003-12-23 | 2004-01-28 | Innomed Ltd | Compositions |
FR2865737B1 (en) | 2004-02-03 | 2006-03-31 | Anteis Sa | BIOCOMPATIBLE RETICLE GEL |
US20090215717A1 (en) | 2004-08-05 | 2009-08-27 | Ivax Drug Research Institute Ltd. | Sulfated oligosaccharides |
BRPI0515191A (en) * | 2004-08-13 | 2008-07-08 | Angiotech Internac Ag | pharmaceutical composition, method for augmenting bone or replacing bone loss, method for reducing pain associated with postoperative scarring, method for preventing surgical adhesion, method for enlarging or repairing skin or tissue, method for maintaining eye fluid volume during eye surgery , method for reducing pain associated with osteoarthritis, method for treating gastroesophageal reflux disease, method for treating or preventing urinary incontinence, method for treating or preventing fecal incontinence, implant method and medical device |
US20080050335A1 (en) | 2006-07-25 | 2008-02-28 | Osmotica Corp. | Ophthalmic Solutions |
WO2008020495A1 (en) * | 2006-08-15 | 2008-02-21 | Tokyo Cemical Industry Co., Ltd. | Novel inhibitor |
FR2918276B1 (en) | 2007-07-02 | 2010-01-22 | Anteis Sa | "USE OF A NATURAL POLYSACCHARIDE (S) GEL FOR THE PREPARATION OF AN INJECTION FORMULATION FOR THE TREATMENT OF JOINT DEGENERESCENCES" |
ITMI20072237A1 (en) | 2007-11-27 | 2009-05-28 | Sigea Srl | MIXED BUTIRRIC-FORMAL ESTERS OF ACID POLYSACCHARIDES, THEIR PREPARATION AND USE AS DERMOCOSMETICS |
US8394784B2 (en) * | 2007-11-30 | 2013-03-12 | Allergan, Inc. | Polysaccharide gel formulation having multi-stage bioactive agent delivery |
FR2924615B1 (en) | 2007-12-07 | 2010-01-22 | Vivacy Lab | HYDROGEL COHESIVE BIODEGRADABLE. |
FR2953522B1 (en) | 2009-12-07 | 2012-03-09 | Fabre Pierre Dermo Cosmetique | SUCROSE ZINC OCTASULFATES, THEIR PREPARATION AND THEIR PHARMACEUTICAL AND COSMETIC APPLICATIONS |
US20110171310A1 (en) | 2010-01-13 | 2011-07-14 | Allergan Industrie, Sas | Hydrogel compositions comprising vasoconstricting and anti-hemorrhagic agents for dermatological use |
FR2956322A1 (en) | 2010-02-17 | 2011-08-19 | Urgo Lab | USE OF SYNTHETIC POLYSULFATE OLIGOSACCHARIDES AS DETERSION AGENTS OF A WOUND. |
US9017712B2 (en) * | 2010-07-12 | 2015-04-28 | Shin Poong Pharmaceutical Co., Ltd. | Filler composition for tissue reinforcement |
FR2983483B1 (en) | 2011-12-02 | 2014-11-14 | Vivacy Lab | PROCESS FOR SIMULTANEOUS SUBSTITUTION AND RETICULATION OF A POLYSACCHARIDE VIA ITS HYDROXYL FUNCTIONS |
-
2012
- 2012-06-13 FR FR1255543A patent/FR2991876B1/en active Active
-
2013
- 2013-06-12 US US13/916,236 patent/US9314530B2/en active Active
- 2013-06-13 AU AU2013276343A patent/AU2013276343B2/en active Active
- 2013-06-13 TR TR2019/07427T patent/TR201907427T4/en unknown
- 2013-06-13 EA EA201492208A patent/EA201492208A1/en unknown
- 2013-06-13 JP JP2015516668A patent/JP6178414B2/en active Active
- 2013-06-13 WO PCT/FR2013/051380 patent/WO2013186493A2/en active Application Filing
- 2013-06-13 CA CA2876057A patent/CA2876057A1/en not_active Abandoned
- 2013-06-13 KR KR20147036186A patent/KR20150023468A/en not_active Application Discontinuation
- 2013-06-13 BR BR112014029510A patent/BR112014029510A2/en not_active IP Right Cessation
- 2013-06-13 MX MX2014013949A patent/MX354544B/en active IP Right Grant
- 2013-06-13 PL PL13733396T patent/PL2861301T3/en unknown
- 2013-06-13 ES ES13733396T patent/ES2728686T3/en active Active
- 2013-06-13 SG SG11201407857SA patent/SG11201407857SA/en unknown
- 2013-06-13 CN CN201380031227.6A patent/CN104394934B/en active Active
- 2013-06-13 EP EP13733396.9A patent/EP2861301B1/en active Active
-
2014
- 2014-11-18 IL IL235776A patent/IL235776A0/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO2013186493A3 * |
Also Published As
Publication number | Publication date |
---|---|
AU2013276343A1 (en) | 2014-12-04 |
US20140005140A1 (en) | 2014-01-02 |
MX354544B (en) | 2018-03-09 |
SG11201407857SA (en) | 2015-02-27 |
CN104394934A (en) | 2015-03-04 |
EA201492208A1 (en) | 2015-04-30 |
FR2991876B1 (en) | 2014-11-21 |
WO2013186493A3 (en) | 2014-05-08 |
KR20150023468A (en) | 2015-03-05 |
FR2991876A1 (en) | 2013-12-20 |
US9314530B2 (en) | 2016-04-19 |
WO2013186493A2 (en) | 2013-12-19 |
CN104394934B (en) | 2018-01-09 |
JP2015525099A (en) | 2015-09-03 |
ES2728686T3 (en) | 2019-10-28 |
IL235776A0 (en) | 2015-01-29 |
AU2013276343B2 (en) | 2017-06-15 |
MX2014013949A (en) | 2015-05-11 |
BR112014029510A2 (en) | 2017-06-27 |
JP6178414B2 (en) | 2017-08-09 |
TR201907427T4 (en) | 2019-06-21 |
EP2861301B1 (en) | 2019-02-20 |
PL2861301T3 (en) | 2020-08-24 |
CA2876057A1 (en) | 2013-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2861301B1 (en) | Composition, in an aqueous medium, including at least one hyaluronic acid and at least one sucrose octasulphate water-soluble salt | |
EP2890360B1 (en) | Sterilised composition comprising at least one hyaluronic acid and magnesium ascorbyl phosphate | |
EP2173324B1 (en) | Hyaluronic acid injectable gel for treating joint degeneration | |
CN103415307B (en) | hyaluronic acid compositions | |
CA2932967C (en) | Hyaluronic acid compositions including mepivacaine | |
EP2187860A1 (en) | Cosmetic or pharmaceutical composition containing hyaluronic acid and cosmetic method for reducing aging signs | |
WO2008148967A2 (en) | Pharmaceutical or cosmetic preparations for topical and/or parenteral application, preparation methods thereof and use of same | |
ES2660847T3 (en) | Mixed butyric formic esters of acidic polysaccharides, and their preparation and use as skin cosmetics | |
FR2977494A1 (en) | Composition, useful for treating skin wounds and irritation in mammals, preferably humans or horses, ophthalmic surgery including glaucoma and cataract, comprises a mixture of hyaluronic acids having different molecular weights | |
CA3127577A1 (en) | Cosmetic/dermatological composition | |
WO2019105718A1 (en) | Anionically charged chitosan | |
FR3074044B1 (en) | CARBOXYALKYL CHITOSANE | |
WO2023198917A1 (en) | Hydrogels for soft tissue filling | |
FR3134577A1 (en) | METHOD FOR PREPARING A HYDROGEL COMPRISING A CROSS-LINKED SILYL POLYSACCHARIDE |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20141218 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
AX | Request for extension of the european patent |
Extension state: BA ME |
|
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
17Q | First examination report despatched |
Effective date: 20170227 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: GRANT OF PATENT IS INTENDED |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61P 19/02 20060101AFI20180316BHEP Ipc: A61K 8/60 20060101ALI20180316BHEP Ipc: A61K 47/36 20060101ALI20180316BHEP Ipc: A61K 31/167 20060101ALI20180316BHEP Ipc: A61Q 19/08 20060101ALI20180316BHEP Ipc: A61K 45/06 20060101ALI20180316BHEP Ipc: A61K 31/7016 20060101ALI20180316BHEP Ipc: A61K 31/728 20060101ALI20180316BHEP Ipc: A61K 8/73 20060101ALI20180316BHEP Ipc: A61P 27/04 20060101ALI20180316BHEP |
|
INTG | Intention to grant announced |
Effective date: 20180410 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAJ | Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted |
Free format text: ORIGINAL CODE: EPIDOSDIGR1 |
|
GRAL | Information related to payment of fee for publishing/printing deleted |
Free format text: ORIGINAL CODE: EPIDOSDIGR3 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
GRAJ | Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted |
Free format text: ORIGINAL CODE: EPIDOSDIGR1 |
|
GRAL | Information related to payment of fee for publishing/printing deleted |
Free format text: ORIGINAL CODE: EPIDOSDIGR3 |
|
GRAR | Information related to intention to grant a patent recorded |
Free format text: ORIGINAL CODE: EPIDOSNIGR71 |
|
INTG | Intention to grant announced |
Effective date: 20180410 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: GRANT OF PATENT IS INTENDED |
|
INTC | Intention to grant announced (deleted) | ||
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE PATENT HAS BEEN GRANTED |
|
INTG | Intention to grant announced |
Effective date: 20180912 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D Free format text: LANGUAGE OF EP DOCUMENT: FRENCH |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 1055993 Country of ref document: AT Kind code of ref document: T Effective date: 20181115 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602013045543 Country of ref document: DE |
|
PUAC | Information related to the publication of a b1 document modified or deleted |
Free format text: ORIGINAL CODE: 0009299EPPU |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: GRANT OF PATENT IS INTENDED |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PK Free format text: LA DELIVRANCE DU BREVET A ETE REVOQUEE PAR L'OEB. |
|
DB1 | Publication of patent cancelled |
Effective date: 20181207 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE PATENT HAS BEEN GRANTED |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
REG | Reference to a national code |
Ref country code: LU Ref legal event code: HK Effective date: 20190103 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 1055993 Country of ref document: AT Kind code of ref document: T Effective date: 20190315 |
|
RAP2 | Party data changed (patent owner data changed or rights of a patent transferred) |
Owner name: LABORATOIRES VIVACY |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190224 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190224 Ref country code: RS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MP Effective date: 20190220 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP Ref country code: CH Ref legal event code: PK Free format text: LA DELIVRANCE DU 24.10.2018 A ETE REVOQUEE PAR L'OEB. |
|
REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG4D |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: MICHELI AND CIE SA, CH Ref country code: CH Ref legal event code: PCOW Free format text: NEW ADDRESS: 44 RUE PAUL VALERY, 75116 PARIS (FR) Ref country code: DE Ref legal event code: R082 Ref document number: 602013045543 Country of ref document: DE Representative=s name: BOHMANN, ARMIN, DIPL.-BIOL.UNIV. DR.RER.NAT., DE Ref country code: DE Ref legal event code: R081 Ref document number: 602013045543 Country of ref document: DE Owner name: LABORATOIRES VIVACY, FR Free format text: FORMER OWNER: LABORATOIRES VIVACY, 74160 ARCHAMPS, FR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: NO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190520 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190520 Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190613 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MK05 Ref document number: 1055993 Country of ref document: AT Kind code of ref document: T Effective date: 20190220 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2728686 Country of ref document: ES Kind code of ref document: T3 Effective date: 20191028 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602013045543 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SM Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
26N | No opposition filed |
Effective date: 20191121 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
REG | Reference to a national code |
Ref country code: BE Ref legal event code: MM Effective date: 20190630 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190613 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190630 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LV Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190220 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190220 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20130613 Ref country code: MT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20190220 |
|
P01 | Opt-out of the competence of the unified patent court (upc) registered |
Effective date: 20230513 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: PL Payment date: 20230612 Year of fee payment: 11 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20230801 Year of fee payment: 11 Ref country code: CH Payment date: 20230702 Year of fee payment: 11 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20240513 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20240606 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20240629 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: TR Payment date: 20240603 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20240618 Year of fee payment: 12 |